• Xuya Huang, Fiona Catherine Moreton, Dheeraj Kalladka, Bharath Kumar Cheripelli, Rachael MacIsaac, R Campbell Tait, and Keith W Muir.
• From the Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom (X.H., F.C.M., D.K., B.K.C., K.W.M.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (R.M.); and Haematology Department, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom (R.C.T.).
• Stroke. 2015 Dec 1; 46 (12): 3543-6.

Background And PurposeWe compared the fibrinolytic activity of tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and intracerebral hemorrhage.MethodsVenous blood samples from a subgroup of participants in the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study were obtained at pretreatment, 3 to 12 hours, and 24±3 hours post-intravenous thrombolysis for analyses of plasminogen, plasminogen activator inhibitor-1, d-dimer, factor V, fibrinogen, and fibrin(ogen) degradation products, in addition to routine coagulation assays. Related sample Wilcoxon signed-rank tests were used to test the within-group changes, and independent Mann-Whitney tests for between-group differences.ResultsThirty patients were included (alteplase=14 and tenecteplase=16) with similar baseline demographics. Compared with baseline, alteplase caused significant hypofibrinogenaemia (P=0.002), prolonged prothrombin time (P=0.011), hypoplasminogenaemia (P=0.001), and lower factor V (P=0.002) at 3 to 12 hours after administration with persistent hypofibrinogenaemia at 24 hours (P=0.011), whereas only minor hypoplasminogenaemia (P=0.029) was seen in the tenecteplase group. Tenecteplase consumed less plasminogen (P<0.001) and fibrinogen (P=0.002) compared with alteplase.ConclusionsIn patients with acute ischemic stroke, alteplase 0.9 mg/kg caused significant disruption of the fibrinolytic system, whereas tenecteplase 0.25 mg/kg did not, consistent with the trend toward lower intracerebral hemorrhage incidence with tenecteplase in the ATTEST study.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01472926.© 2015 American Heart Association, Inc.

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